Eating Disorder Lecture Flashcards
(65 cards)
1
Q
What is the definition of ‘Eating Disorders (ED)’?
A
A persistent disturbance of eating that results in the altered consumption or absorption of food and that significantly impairs physical health or psychosocial functioning.
2
Q
How can ED severely affect the relationship between food and body image?
A
1) Excessive thoughts for food.
2) Body weight or shape concerns.
3) Control of food intake.
3
Q
What are the main types of eating disorders?
A
(1) Anorexia nervosa (weight loss, extreme dieting, starvation, too much exercise)
(2) Bulimia nervosa (binge eating followed by purging, taking laxatives, excessive exercise, fasting to avoid weight gain)
(3) Binge eating (frequently consume an unusually large amount of food in a brief amount of time (no purging).
4
Q
What is the average age of onset for Anorexia Nervosa in Canada?
A
1) The average age of onset for Anorexia Nervosa is 16 - 17 years old.
2) More than 10% of girls met the criteria for eating disorders between 13 and 20 years old.
5
Q
What mental illness has the highest mortality rate?
A
- ED (10-25%)
- Around 20% of ED results in premature death.
6
Q
What group of people to ED effect?
A
- all community, regardless of gender, age, racial and ethnic identify, sexual orientation or socio-economic background.
7
Q
What is Anorexia Nervosa (AN)?
A
Anorexia Nervosa is characterized by persistent restriction of energy intake, leading to significantly low body weight, and an intense fear of gaining weight.
8
Q
What are the two subtypes of Anorexia Nervosa?
A
(1) Restricting type (AN-R): Weight loss accomplished by dieting, fasting, and excessive exercise.
(2) Binge Eating-Purging type (AN-BP): Recurrent episodes of binge eating followed by self-induced vomiting or misuse of laxatives, diuretics, or enemas to compensate for food intake.
9
Q
How does Anorexia Nervosa impact body weight?
A
It results in significantly low body weight.
10
Q
What is Bulimia Nervosa (BN)?
A
Bulimia Nervosa is characterized by binge eating (eating a large amount of food in a short period) followed by purging (vomiting or using laxatives) to get rid of the consumed food.
11
Q
What is the weight status of individuals with Bulimia Nervosa?
A
Individuals with Bulimia Nervosa are typically of normal weight or overweight.
12
Q
Who is most affected by Anorexia Nervosa (AN) and Bulimia Nervosa (BN)?
A
Women.
13
Q
What is Binge-Eating Disorder (BED)?
A
Binge-Eating Disorder is characterized by compulsive overeating or consuming large amounts of food while feeling a loss of control, without any action to eliminate the calories consumed.
14
Q
Who is most affected by Binge-Eating Disorder (BED)?
A
Both genders equally.
15
Q
What is the main difference between AN-BP and BN?
A
The main difference is that individuals with AN-BP experience weight loss of more than 15%, while BN does not typically involve significant weight loss.
16
Q
How is anorexia caused by conditions like cancer or depression different from anorexia nervosa?
A
Anorexia caused by conditions like cancer or depression is considered anorexia but not anorexia nervosa, as it is a symptom of those conditions rather than a primary disorder.
17
Q
What is Pica?
A
Pica is the persistent eating of non-nutritive substances, such as dirt or paint, for at least one month.
18
Q
What is Rumination Disorder?
A
Rumination Disorder is a condition where individuals repeatedly and unintentionally regurgitate undigested or partially digested food from the stomach, rechew it, and either reswallow it or spit it out. It typically occurs in infants and very young children (3-12 months) and lasts for at least one month.
19
Q
Is obesity considered a mental disorder?
A
No
20
Q
What is Avoidant Restrictive Food Intake Disorder (ARFID)?
A
ARFID is a restrictive food intake disorder where individuals do not have the drive for thinness or distress about body shape or fears of fatness, unlike anorexia.
21
Q
What is the mortality rate associated with Anorexia Nervosa (AN)?
A
The mortality rate associated with Anorexia Nervosa is 12 times greater than that of all other causes of death combined.
22
Q
What are the causes of death in patients with Anorexia Nervosa?
A
- The causes of death in patients with AN include suicide, multi-organ failure, cardiovascular complications, and sudden death.
- Anorexia Nervosa has a mortality rate of about 5-10% per decade, primarily due to suicide and cardiac arrest.
23
Q
What is the rank of Anorexia Nervosa among psychiatric conditions affecting adolescent girls?
A
Anorexia Nervosa is the third most common psychiatric condition affecting adolescent girls, after depression and anxiety.
24
Q
What other mental health disorders are often associated with Anorexia Nervosa?
A
Anorexia Nervosa is associated with high levels of major depressive disorder, anxiety disorder, post-traumatic stress disorder, and substance use disorders.
25
How is weight loss and BMI used to diagnose the severity of Anorexia Nervosa?
- Weight loss of more than 15% of ideal body weight is a key indicator for Anorexia Nervosa.
- A weight loss of more than 25% typically requires hospitalization.
- Body Mass Index (BMI) is a reliable indicator, calculated as BMI = weight (kg) / height (m²).
- Normal BMI: 18-25.
- BMI below 17.5 in adults is a common physical characteristic used to diagnose Anorexia Nervosa.
- Severity index of Anorexia Nervosa based on BMI:
a) Mild: BMI < 17.5
b) Moderate: BMI 16-16.99
c) Severe: BMI 15-15.99
d) Extreme: BMI < 15
- BMI between 15-18.5 is associated with a 50% increased risk of death.
26
What are the symptoms/characteristics of AN?
(1) Alteration of body image: feeling too fat, a negative distortion of self-body image.
(2) Intense fear to gain weight, aversion for caloric food.
(3) Minimization and denial of the seriousness of low-body weight.
(4) Anorexia often associated with physical or intellectual hyperactivity (over-accomplishers).
(5) Lack of cognitive flexibility.
27
What are the physical consequences of AN?
(1) Physical Symptoms:
- Heightened sensitivity to cold
- Gastrointestinal symptoms: constipation, fullness after eating, bloating
- Dizziness and syncope
- Amenorrhoea, low sexual appetite, infertility
- Poor sleep with early morning waking
(2) Physical Signs:
- Emaciation, stunted growth, failure of breast development (if onset is prepubertal)
- Dry skin, fine downy hair (lanugo) on the back, forearms, and face
- Orange discoloration of palms and soles (hypercarotenaemia)
- Swelling of parotid and submandibular glands (especially in bulimic patients)
- Erosion of inner surface of front teeth (perimylolysis)
- Cold hands and feet, hypothermia
- Bradycardia, orthostatic hypotension, cardiac arrhythmias
- Dependent oedema, weak proximal muscles (difficulty rising from a squat)
(3) Abnormalities on Physical Investigation:
- Endocrine: Low LH, FSH, oestradiol, low T3, T4 (normal TSH), mild increase in plasma cortisol, raised growth hormone, low leptin
- Cardiovascular: ECG abnormalities (prolonged Q-T interval, conduction defects)
- Gastrointestinal: Delayed gastric emptying, decreased colonic motility (due to laxative misuse), acute gastric dilatation (from binge eating/re-feeding)
- Haematological: Moderate normocytic normochromic anaemia, mild leucopenia with relative lymphocytosis, thrombocytopenia
- Metabolic: Hypercholesterolaemia, raised serum carotene, hypophosphataemia (especially during refeeding), dehydration, electrolyte disturbances
- Other: Osteopenia, osteoporosis (increased fracture risk), enlarged cerebral ventricles (pseudoatrophy)
*** early onset anorexia nervosa have long lasting consequences***
28
What are the consequences of Anorexia Nervosa on the brain?
(1) Alterations in brain development:
(a) Enlarged cerebral ventricles and external cerebrospinal fluid spaces (pseudoatrophy)
(b) Reductions in brain size (possible loss of brain cells and connections)
(c) Reduction of cortical thickness, subcortical volumes, and cortical surface area
(d) Widespread white matter abnormalities
(2). Altered brain connections:
(a) Disrupted thalamo–cortical and occipital–parietal–temporal–frontal white matter connections
(b) Studies using diffusion tensor imaging have shown these alterations in both anorexia and bulimia nervosa.
29
What are the psychological consequences of Anorexia Nervosa?
(1) Long term psychological and social problems.
Depression
Anxiety
Obsessive-compulsive disorder
Social phobia
Substance abuse
Suicide
30
Describe the evolution of Anorexia Nervosa after 18-20 years old:
- 30% experience complete remission with brief intervention.
- 30% retain abnormal eating behaviors and need intensive treatment.
- 30% become chronic, with a poor prognosis and treatment resistance.
- Severe long-term starvation causes irreversible damage to the body and brain, leading to obsessive and manipulative behaviors.
- Conclusion: The disorder worsens with age, resulting in a high mortality rate.
31
What are the current treatments for AN?
(1) Antidepressant (SSRI help alleviate alleviate depression, anxiety, or obsessive thinking)
(2) Psychotherapy:
Psychological counseling, Psychotherapy, Group therapy, psychanalysis, Cognitive behavioral therapy to recognize and change distorted or maladaptive thinking about food
(3) Neuroleptics/Nutrionial support.
There is low success rate. There is no specific biological therapy/treatments are needed for chronic patients. There is absence of safe, efficient and specific treatment.
32
What are the causes of AN?
Causes are unknown: combination of psychodynamic, sociocultural and genetic factors.
Since we hardly understand causes, we lack specific and efficient treatments to improve the success rate of Psychological and nutritional interventions.
33
What contributes to AN?
(1) Genes: Twins studies suggest that anorexia nervosa is ≈ 50-80% heritable* (suggest that there is a strong genetic and neurobiological basis underlying AN)
(2) Environmental factors: magazines, Web sites, peer and cultural/social pressure
(3) Personality traits: perfectionism, body dissatisfaction, obsessive thoughts and behaviors OCD ?
(4) Other risk factors: past history of anxiety, depression, or substance abuse, or physical or sexual abuse, low self-esteem.
34
How can we understand and treat AN?
1) To specifically treat AN we need to understand underlying neurobiological mechanisms.
2) To understand AN we need to combine pre-clinical and clinical investigation.
3 step process:
a) Develop an animal model (rodents) of endophenotypes of Anorexia.
b) Establish neurobiological causes => treatment.
c) Test new hypotheses in patients.
35
What are the key characteristics of anorexia nervosa related to behavior and cognitive functioning?
- Aberrant reward processing (delay discounting).
- Lack of cognitive flexibility.
- Loss of behavioral control and compulsive self-starvation.
- Inability to interrupt behavior despite negative consequences (lack of sensibility to contingency degradation).
- Common basis with compulsive disorders.
- Theory suggests AN = excessive habit formation or difficulty regaining control over habits.
- Compulsive behaviors result from an imbalance between goal-directed behaviors and habit-driven behaviors.
36
What is the definition of compulsion?
- An uncontrollable urge to say or do something without an obvious reason, over and over independently from negative consequences.
- A compulsion is an « unconscious » automatic behavior.
- Fundamentally, compulsion is an imbalance between goal directed behaviors and habits.
- Compulsion is the core of obsessive-compulsive disorders.
37
Goal directed behaviours, habit formation, and compulsion, what brain area pilots these functions?
Striatum
38
What is the difference in composition of the striatum in humans and in mice?
(1) Humans:
- Nucleus accumbens
- Caudate nucleus
- Putamen
(2) Mice:
- Nucleus accumbens
- Dorsomedial striatum (caudate in humans)
- Dorsolateral striatum (putamen in human)
39
What are the motor and cognitive functions of the striatum?
1) Elaboration and repetition of voluntary movement.
2) Reward processing: Piloted by the Nucleus Accumbens.
3) Goal-directed behavior (GDB): Piloted by the caudate.
--> Behavior oriented toward attaining a specific goal.
---> Sensitive to outcome reward value and contingency.
4) Habit formation: Piloted by the putamen.
---> Automatic behavior.
---> Insensitive to reward devaluation and contingency degradation.
5) Goal-directed behaviors: Driven by the expectation of reinforcement with desirable outcomes (conscious behavior).
6) Habits: Stimulus-response associations that are insensitive to reward or consequences (automatic behavior).
40
How does the striatum transition from reward to goal-directed behavior to habits and finally to compulsion?
(1) Normal Striatum Function:
-> Nucleus Accumbens: Reward
-> Dorsomedial striatum (DMS) (caudate): goal-directed behaviour.
-> Dorsolateral striatum (DLS) (putamen): habit formation and automaization (learning)
(2) Pathological transition:
-> Excessive habit formation or difficulty regaining control leads to compulsion.
-> Loss of control can result in disorders like addiction, anorexia, bulimia, and compulsive behaviours.
41
What role does the striatum play in psychiatric disorders with a compulsive dimension?
The striatum is key in understanding and treating psychiatric disorders with compulsive behaviors, including:
1) Gilles de la Tourette syndrome (Tic)
2) Addiction
3) Obsessive-compulsive disorders (OCD)
4) Eating disorders (ED)
42
Describe the flow of information in neurons.
- neurons are highly asymmetrical polarized cells specialized in communication.
- neurons exchange information with themselves, other neurons, the entire body, the outer world.
43
What are the 5 steps of neurotransmission?
1) Synthesis of neurotransmitters.
2) Storage of synaptic vesicles.
3) Release.
4) Action on receptors.
5) Signal interruption (diffusion, degradation or re-uptake)
44
What are synapses?
- They are strategic areas of the brain where neurons "talk" to each other.
45
What is the role of vesicular glutamate transporters (VGLUTs) in glutamatergic transmission?
(1) VGLUTs are crucial for glutamatergic transmission.
Without VGLUTs, glutamatergic neurons are “silent,” meaning they do not release glutamate and cannot transmit signals.
(2)
VGLUT1 and VGLUT2 are expressed in classical glutamatergic neurons:
--> VGLUT1: Predominantly in cortical neurons.
--> VGLUT2: Found in subcortical neurons.
(3) VGLUT3: Expressed in heterologous neurons that use other neurotransmitters, including: (strong expression in the striatum)
--> Cholinergic interneurons in the striatum (Chls).
--> GABA interneurons in the hippocampus and cortex.
--> Serotonin neurons in the raphe nuclei.
46
What are the major neurotransmitters in the striatum?
- constituted by a large population of GABA (inhibitory) neurons named medium spiny neurons (MSN). (90%)
- GABAergic interneurons. (1%)
- Cholinergic interneurons (ChIs) (1%)
- The striatum receives a massive glutamatergic projection from the cortex and the thalamus.
- A massive dopaminergic projection (DA) from the SNC/VTA
47
What is the cortico-striatal-cortical loop?
The cortico-striatal-cortical loop is a key part of the brain's network that helps control movement, behavior, and decision-making. This loop connects the cortex (which is involved in higher-level thinking and planning) with the striatum (which plays a major role in motor control and habit formation), and then loops back to the cortex.
The loop operates similarly across different compartments of the striatum. These compartments manage reward processing, decision-making, and motor control, ensuring that the striatum responds appropriately to both rewards and external stimuli.
48
What is the role of dopamine (DA) in the cortico-striatal-cortical loop?
- Dopamine (DA) is a critical neurotransmitter in this loop. It binds to two types of receptors in the striatum:
- D1 receptors activate the GO pathway, promoting goal-directed behavior (GDB), reward-seeking actions, and habit formation. This helps with the initiation of actions and moving toward rewards.
- D2 receptors inhibit the NOGO pathway, which suppresses unnecessary or unwanted behaviors, helping to prevent actions that are not beneficial.
- The balance between D1 and D2 receptor activation helps guide behavior toward achieving goals or rewards, and to stop behaviors that are not productive or harmful.
49
What is the effect of dopamine on behaviour?
1) When there is too much dopamine, the system becomes overactive, favoring reward-seeking behaviors, goal-directed actions, and the formation of habits. This can contribute to behaviors seen in addiction, compulsions, or excessive habitual actions.
2) On the other hand, not enough dopamine (as seen in Parkinson's disease) leads to reduced movement initiation, lack of motivation, and difficulty in forming goal-directed behaviors.
50
What are cholinergic interneurons (Chls) and what are their role?
- Cholinergic interneurons in the striatum are involved in regulating the striatal network, though their exact role is more complex and not fully understood.
- Unique because they can release two neurotransmitters:
1) Acetylcholine (ACh): involved in modulating motor control and learning.
2) Glutamate: a major excitatory neurotransmitter, involved in synaptic plasticity and strengthening neural connections.
ChIs are called "bilingual" because they use both acetylcholine and glutamate, enabling them to regulate both motor and cognitive functions in a nuanced way.
51
What are the molecular consequences of VGLU3 expression in Chls?
(1) ChIs co-release acetylcholine and glutamate.
(2) Increases vesicular accumulation of acetylcholine (vesicular synergy) and increase cholinergic transmission.
- VGLUT3 provides Chls with 2 properties:
a) Glutamate transmission.
b) Increased ACh transmission (vesicular synergy)
52
Where is VGLUT3 abundantly expressed and what is the significance of this?
- Striatum
- Involved in compulsive disorders: addiction, eating disorders, obsessive compulsive disorders (TOC).
53
What is the significance of rare VGLUT3 variants in addiction and psychosis?
- VGLUT3 rare variants are associated with severe addiction in humans.
- Frequency of VGLUT3-p.T8I allele:
0.5% in control population
5% in individuals with addiction
- Characterization:
VGLUT3-p.T8I carriers were not different from other addicts.
Psychosis observed in some patients, indicated by higher SAPS scores (Schizophrenia Assessment Scale).
54
What biochemical changes are associated with the VGLUT3-p.T8I mutation?
- Does not alter vesicular glutamate uptake or release.
- Blunts vesicular synergy (reduces efficiency of vesicle functions).
- Reduces ACh content in synaptic vesicles.
- Reduces ACh release in the striatum in VGLUT3T8I/T8I mice.
55
How does the VGLUT3-p.T8I mutation affect dopamine release and signaling in the striatum?
- Reduces dopamine release in the caudate (DMS).
- No change in dopamine release in the putamen (DLS).
- Leads to uneven dopamine signaling in the striatum:
--> Less dopamine released in the caudate (DMS).
--> Relatively more dopamine in the putamen (DLS).
56
How do VGLUT3T8I/T8I mice behave in a “normal” environment, and what are their tendencies regarding habit formation?
(1) VGLUT3T8I/T8I mice in a normal environment behave normally with no obvious phenotypes.
(2) Habit formation:
- Not sensitive to reward devaluation (meaning they continue their behavior even when the reward is no longer desirable)
- More prone to form excessive habits due to altered reward processing.
57
How is compulsive grooming assessed in VGLUT3T8I/T8I mice, and what do the results indicate?
(1 )Compulsive grooming is assessed using the splash test, where a 10% sucrose solution is sprayed on the mouse's body.
(2) Recording of grooming episodes: The number of grooming behaviors (licking, biting, scratching) is observed.
(3) Results: VGLUT3T8I/T8I mice exhibit more vulnerable compulsive grooming behavior, which is used as a model for obsessive-compulsive disorder (OCD).
58
What is the cocaine administration model used in VGLUT3T8I/T8I mice, and what does it reveal about their vulnerability?
(1) In the cocaine administration model, VGLUT3T8I/T8I mice receive 0.5 mg/kg of cocaine through infusion sessions lasting 2 hours per day.
(2) Results: VGLUT3T8I/T8I mice are more vulnerable to cue-induced relapse (they are more likely to relapse into cocaine-seeking behavior after cues associated with the drug).
59
What does the term "Cue-R" refer to in behavioral testing, and how does it relate to the VGLUT3T8I/T8I mice's behavior?
(1) Cue-R stands for Cue-induced reinstatement, which tests the animal's behavior in response to a cue previously associated with a rewarding experience (like cocaine).
(2) VGLUT3T8I/T8I mice are more susceptible to this cue-induced relapse, suggesting a compulsive behavior pattern similar to addiction.
60
What are the differences between the Fixed Ratio (FR) and Progressive Ratio (PR) in behavioral tests?
(1) Fixed Ratio (FR): Reinforcements are given after a set number of responses, measuring the animal's response rate.
(2) Progressive Ratio (PR): The number of responses required for reinforcement increases progressively, often used to measure motivational aspects of behavior and addiction.
(3) Both methods can be used to assess compulsive behavior, with VGLUT3T8I/T8I mice showing altered patterns in response to these tests.
61
How can Anorexia nervosa be modeled in rodents, and what are the key findings in the Activity-Based Anorexia (ABA) model regarding VGLUT3 T8I/T8I mice?
(1) Modelling:
- The Activity-Based Anorexia (ABA) model creates a conflict between eating and running.
- Rodents have free access to a running wheel and food for 7 days (habituation phase).
- Afterward, there is progressive food restriction over 8 days while maintaining access to the running wheel.
- Key Measurement: The number of mice falling below 75% of their normal body weight.
(2) Findings:
- VGLUT3 T8I/T8I mice are more vulnerable to self-starvation in the ABA model.
- These mice show greater susceptibility to the self-destructive behavior characteristic of anorexia.
62
How is bulimia-like behavior modeled in rodents, and what are the key findings in VGLUT3 T8I/T8I mice?
(1) Modeling:
- Mice undergo 20-hour food restriction overnight.
- At 8 AM, they are given 4 hours of binge-like sucrose consumption (access to sucrose water).
(2) Findings:
- VGLUT3 T8I/T8I mice are more vulnerable to binge-like sucrose over-consumption, a behavior similar to bulimia.
- These mice show an increased tendency for excessive eating during the binge period.
63
How can acetylcholine (ACh) transmission be restored in VGLUT3 T8I/T8I mice, and what is the impact on eating disorders and compulsive behaviors?
(1) Restoring ACh Transmission in VGLUT3 T8I/T8I Mice:
a) VGLUT3 T8I/T8I mice have decreased ACh, causing uneven dopamine (DA) transmission.
b) Prediction: Restoring ACh transmission could help abolish eating disorders in VAChT knockout (VAChTcKO) mice.
c) Approach: Increasing ACh using AChE inhibitors (e.g., Donepezil).
64
What are the effects of Donepezil?
- Donepezil is an acetylcholinesterase inhibitor, preventing ACh degradation and increasing ACh tone.
- Donepezil reverses compulsive grooming in VGLUT3 T8I/T8I mice.
- Donepezil reduces “anorexia”-like behaviors in VGLUT3 T8I/T8I mice.
- No effect observed in wild-type (WT) mice.
65
Can Donepezil be used to treat anorexia nervosa (AN) in humans, and what were the results of the small clinical case study?
- A small clinical case study was conducted to assess the effectiveness of Donepezil (an acetylcholinesterase inhibitor) in treating anorexia nervosa (AN).
- All patients gained weight and showed an increase in BMI.
- Improvement in Eating Disorder Symptoms: All patients showed improvement in all aspects of eating disorders.
- All patients (except 1) showed improvement in mood disorders (anxiety, depression) and compulsivity.
- Reduced compulsive behaviors were observed in patients.
